title: Clinical trial results with hirudin and bivalirudin for acute coronary artery syndromes.
abstract: Thrombin plays a key role in the pathophysiology of acute coronary artery syndromes. The "thrombin hypothesis" states that more complete and consistent thrombin inhibition may improve clinical outcomes in acute ischemic syndromes. The direct thrombin inhibitors hirudin and bivalirudin are potentially superior agents to heparin and have been tested in several clinical trials. More predictable and less variable levels of anticoagulation have been demonstrated. Adverse clinical events have been reduced during active treatment with hirudin or bivalirudin, but increased bleeding, including intracerebral hemorrhage, can occur with excessive anticoagulation. Unfortunately, the short-term benefit has not been sustained during follow-up. The multiplicity of pathways for platelet activation, inadequate treatment duration, or the inability to block thrombin generation may explain the limited efficacy. In contrast, inhibitors of the glycoprotein IIb/IIIa platelet receptor are associated with a more dramatic and durable reduction in clinical events.
authors.affiliation: Department of Medicine, University of Michigan, Ann Arbor, USA.
authors.forename: E R
authors.initials: ER
authors.lastname: Bates
mesh_terms: D000789:Angina, Unstable / Q000188:drug therapy; D015906:Angioplasty, Balloon, Coronary; D000991:Antithrombins / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D003327:Coronary Disease / Q000188:drug therapy*; D024764:Hirudin Therapy; D006629:Hirudins / Q000031:analogs & derivatives*; D006801:Humans; D010446:Peptide Fragments / Q000627:therapeutic use*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism; D011994:Recombinant Proteins / Q000627:therapeutic use; D013577:Syndrome
chemical_list: D000991:Antithrombins; D006629:Hirudins; D010446:Peptide Fragments; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011994:Recombinant Proteins; C074619:bivalirudin